Driving change in chronic lymphocytic leukaemia (CLL)

Becky, our senior medical writer, provides the latest instalment from the 2017 meeting of the American Society of Hematology.

The ASH (American Society of Hematology) meeting in December is the largest gathering of lymphoma experts worldwide. In January, UK experts met in London to talk about the latest developments presented at ASH and their implications for clinical practice in the UK.

In this, our fourth summary, we are looking at newer drugs, new treatment goals and new guidelines that are driving change in chronic lymphocytic leukaemia (CLL).

We recently reported on updates in CLL research and management of this chronic (long-term) condition. New guidelines for the management of CLL are being developed by the British Society of Haematology and will bring new treatments into standard practice.

The targeted drug ibrutinib is now standard treatment for people with genetic mutations (changes) in the abnormal cells that make CLL difficult to treat. It is also an important option when CLL relapses (comes back), if it doesn’t respond to chemotherapy and for some people with health conditions that mean chemotherapy is not suitable for them. Idelalisib can be given for people who can’t have ibrutinib and venetoclax is becoming increasingly available if these options don’t work. Research is ongoing to see how these newer drugs can best be used and whether combinations of newer drugs could replace chemotherapy as a first treatment for CLL.

Taking drugs every day long-term is expensive, can have side effects and can lead to people stopping treatment before they are in a good remission. Many clinical trials are testing whether people who have a complete response (no evidence of CLL) to newer drugs can stop treatment without CLL flaring up again.

The CLARITY trial showed that the combination of ibrutinib and venetoclax gives high response rates and can completely clear CLL in some people who have already received other treatments. Following on from this, the FLAIR trial is testing whether standard chemotherapy, ibrutinib alone, ibrutinib with rituximab, or ibrutinib with venetoclax gives the best outcomes for people with untreated CLL. FLAIR is still recruiting people in the UK.

As ibrutinib is becoming more widely used, research studies are giving important information about the ongoing effects of this long-term treatment. One concern is the risk of infections while on ibrutinib. A study of 566 people with low-grade lymphomas. where the majority had CLL, showed that the risk of infection was low, with only 4.7% (around 1 in 21 people) developing infections in 5 years.

Venetoclax is becoming increasingly important as a treatment for CLL. It is currently used if other newer drugs have failed to keep CLL under control. However, the phase 3 MURANO trial showed that more than twice as many people treated with venetoclax and rituximab (82.8%) were still in remission (CLL did not get worse) 2 years after treatment, compared with standard treatment of bendamustine and rituximab (37.4%). Perhaps venetoclax will be used for earlier relapses in the future.

With new approaches improving outcomes for people with CLL, the biggest treatment challenge is Richter’s Syndrome. Richter’s happens when CLL transforms (changes) from growing slowly to growing quickly. It is challenging to treat and new approaches are urgently needed.

To read more new stories about clinical trials and to find a trial that might be suitable for you, visit Lymphoma TrialsLink.